Patients presenting with chest pain pose major diagnostic and therapeutic challenges. One of the challenge is to determine if the cause of the chest pain is something benign like muscular pain or it is because of arterial blockage leading to obstruction in blood supply and hence death of heart muscle. The Electrocardiogram (ECG) test is helpful in certain cases if there is clear-cut evidence of heart attack. However, ECG test may not be very helpful in a vast majority of cases in separating the muscular pain from the more dangerous cardiac pain. In such cases diagnosis and treatment becomes difficult for patients with a suspected heart disease e.g. who have non-diagnostic electrocardiograms.
For most emergency physicians it is desirable to have a highly sensitive and highly specific test for detection of acute coronary syndrome for making diagnostic and therapeutic decisions at the right time, particularly within a relatively short period of time following the onset of chest pain. Various serum markers such as creatine Kinase (CK) and its more cardiac specific isoenzymes (CK-MB) were used for diagnosis of acute myocardial infarction. CK-MB has been a preferred marker for many years due to high specificity for cardiac tissues of MB fraction of CK. However, false positive results may occur due to presence of e.g. CK-MB released from skeletal muscle, myopathies, hypothyroidism etc. A reported disadvantage of the CK-MB is delayed diagnosis and poor prognostic index. A pattern of rise and fall may take about 10-30 hours, requiring serial determinations over a period of 24 hours. Marker such as cardiac Troponin T and I are highly specific for cardiac problems e.g. myocardial injury. These proteins are not present in smooth muscle and in the blood of normal healthy human subjects. For the purpose of diagnosis, the problem of false positives has been reported with Troponin. Troponins may be helpful for patients in which CK-MB is elevated due to release from skeletal muscle. It is also reported in the literature that elevated serum plasma Troponins provide useful prognostic information. Elevated levels of either cTnT or cTnI may indicate a much higher chances of adverse cardiac outcomes. Across the acute coronary syndrome spectrum, patients with ST elevation myocardial infarction are the easiest to identify and hence early management strategies are well defined. Non ST elevation myocardial infarction patients also benefit from early invasive strategies but the intervention is usually delayed up to 24 hours due largely in part because of the absence of a predictable early biomarker in the setting of non-diagnostic electrocardiogram. Some of the studies suggests that Troponins are useful for the evaluation of patients with chest pain in the emergency department (ED), however they may not be utilized as a sole criteria e.g. in cases with negative Troponin values especially when a patient presents early after onset of chest pain.
Over the years, cardiac biomarkers have been evaluated for multiple clinical purposes such as screening for preclinical disease, diagnosis of disease in patients with nonspecific symptoms and non-diagnostic electrocardiograms, risk stratification in patients with clinical disease and as a guide in selection of appropriated therapeutic options. The commonly used biomarker called Troponin I or Troponin T both detect death of heart muscle or myonecrosis. The test however comes positive six to twelve hours after the onset of the pain even if there is muscle necrosis. Thus, from the time of onset of chest pain for up to six hours there is no reliable way of separating cardiac chest pain from non-cardiac chest pain. In such situations patients are admitted and observed as if they have a heart attack until a more accurate assessment may be made at e.g. twelve hours. Thus, not only is the diagnosis delayed adding to hospital costs but important treatments like dual anti-platelet therapy and angioplasty are also delayed until a correct diagnosis may be established. Diagnostic tests have been developed to determine whether or not the source of the chest pain is cardiac or whether the human subject has suffered some heart problem e.g. a myocardial infarct or unstable angina. However, these tests do not provide sufficient information for an early detection of ACS and information useful for prognosis. The term ‘prognosis’, herein relates to methods for predicting the outcome of pathology or for predicting the probability or likeliness that an adverse outcome will be observed in a patient.
It is desirable to identify a sensitive, cardiac specific and early detectable marker which bears a close relation to the extent of cardiac problem/damage and which provides prognostic information. Therefore, there is need for reliable methods, apparatuses and biomarkers for early diagnosis or detection of acute coronary syndrome and reliable methods for predicting adverse cardiac events in a setting of acute coronary syndrome.